tbuckley/cabot-search huggingface dataset:
Maxed out: Reaching the annual maximum out-of-pocket limit among insured patients diagnosed with cancer.
Authors: Matthew P. Banegas, John F. Dickerson, Amanda F Petrik, Melissa L. Anderson, Erin Keast, Arvind Ramaprasan, Jamie Wallace, Nora B. Henrikson
Journal: Journal of Clinical Oncology (2023)

6646 Background: Patients with cancer face potentially high out-of-pocket costs associated with their medical care, which may lead to adverse medical and financial outcomes. Depending on their health insurance plan, patients may have to pay several thousands for medical care costs until they reach the annual maximum out-of-pocket [MOOP] spending limit; after which care costs are covered by insurance. The purpose of this study was to measure the proportion of adult patients who reach their health plan MOOP limit in the year of cancer diagnosis. Methods: Electronic health record data from 13,057 patients aged ≥18 years, diagnosed with cancer between Jan. 1, 2016–March 31, 2021 [index cancer], with ≥12 months of continuous health insurance coverage pre-cancer diagnosis were included. The primary outcome was defined as reaching the MOOP limit in the health plan benefit year of index cancer diagnosis (binary, yes/no). We additionally created a secondary outcome using 3 categories: (i) did not reach MOOP; (ii) reached MOOP prior to cancer diagnosis; (iii) reached MOOP after cancer diagnosis. Descriptive statistics were used to assess the distribution of outcomes across patient characteristics including health insurance type (e.g., commercial), high-deductible health plan (HDHP), cancer type, age at diagnosis, and Census-level household income was included. Multivariable logistic regression estimated the association between patient characteristics and the primary outcome. Complete case analyses were performed using Stata 16.1. Results: Patients’ mean age was 66 years (standard deviation [sd]: 13) and mean Census-level household income was $73,100 (sd: $24,000). Approximately 40% of patients had commercial health insurance and 62% had Medicare; 2% (n=283) had a HDHP. Breast (18%), lung (11%) and prostate (11%) cancers were most common. The mean annual MOOP limit was $3,040 for commercial plans and $2,688 for Medicare plans. Among patients with a commercial plan insurance, 46% reached their MOOP limit including 8% before and 37% after cancer diagnosis. For Medicare patients, 20% reached their MOOP limit, including 3% before and 17% after cancer diagnosis. Patients with a HDHP (adjusted Odds Ratio [aOR]: 2.61, 95% CI: 1.96-3.47), breast cancer (aOR: 2.29, 95% CI: 1.84-2.84), and lung cancer (aOR: 2.71, 95% CI: 2.04-3.61) had significantly greater odds of reaching the MOOP than those with a non-HDHP and other cancers. Household income was also significantly associated (aOR: 0.97, 95% CI:0.95-0.99) with reaching the MOOP. Conclusions: A substantial proportion of patients reach the annual MOOP limit during the year of cancer diagnosis, representing a population at high-risk for medical financial hardship. Future longitudinal studies are needed to assess the trajectory of OOP spending and implications on care utilization and health outcomes.
Description of technique for endoscopic ultrasound-guided tissue acquisition in pancreatic cancer for comprehensive molecular profiling: Results of a randomized trial.
Authors: Ji Young Bang, Nirag Jhala, Anjali Seth, Konrad Krall, Udayakumar Navaneethan, Robert Hawes, C. Mel Wilcox, Shyam Varadarajulu
Journal: Journal of Clinical Oncology (2023)

e16306 Background: As theoretically actionable genomic lesions are found in almost 50% of pancreatic cancers which can impact clinical management in up to 30% of patients, there is increased focus on molecular profiling. Although EUS-FNB is an established method for achieving pathological diagnosis in pancreatic cancers, the technique of tissue acquisition for comprehensive molecular profiling (CMP) has not been described. Methods: Patients proven to have pancreatic adenocarcinoma using rapid onsite evaluation (ROSE) at EUS were randomized to undergo two or three dedicated FNB passes for CMP. Tissue was procured using 22G Franseen needle adopting the fanning technique and stylet-retraction maneuver. Genomic DNA and total RNA were extracted from formalin-fixed paraffin-embedded (FFPE) cell blocks (Qiagen AllPrep). Next-generation sequencing (NGS) was performed (Archer Panels) for analyzing 69 gene DNA mutations (single nucleotide variants, insertions, and deletions) and 53 RNA somatic oncogenic gene fusions. Main outcome measure was the proportion of specimens in which adequate DNA and RNA were extracted for CMP. Results: 33 patients (mean age 77.0 years [SD 7.7], female = 20) with pancreatic cancer (location = head/uncinate 22; other 11) were randomized to two (n = 17) or three (n = 16) FNB passes. While sufficient DNA was extracted from all 33 FFPE cell blocks, adequate RNA was extracted from 15 of 16 in the three pass (93.8%) vs. 16 of 17 in the two pass cohort (94.1%) (p = 0.99). There was no significant difference in the mean concentration of DNA (two passes 10.7 ng/ul [SD 7.1] vs. three passes 7.9 ng/ul [SD 4.4]; p = 0.19) or RNA (two passes 37.1 ng/ul [SD 26.5] vs. three passes 28.9 ng/ul [SD 13.2]; p = 0.29) between the groups. While somatic oncogene RNA fusion (LDAH-ETV1) predictive of metastatic disease was identified in one specimen, DNA mutations were identified in all 33 specimens that included one BRCA1 mutation that warranted Oxaliplatin-based chemotherapy. Conclusions: Specimens of adequate quantity and of high quality for comprehensive molecular profiling in pancreatic cancer can be procured in nearly 95% of patients by performing two dedicated passes using the 22G Franseen needle, adopting the fanning maneuver and stylet-retraction technique. Clinical trial information: NCT05043532 .
Correlating expression of NaPi2b and FRa in high grade serous ovarian cancer (HGSOC).
Authors: Debra L. Richardson, Minal A. Barve, Erika P. Hamilton, Sara Kristina Taylor, Charles K Anderson, Joseph Buscema, Marilyn Huang, Rebecca Christian Arend, John L. Hays, Premal H. Thaker, Nehal J. Lakhani, Rebecca Mosher, Pamela Shaw, Chelsea Bradshaw, Min Lu
Journal: Journal of Clinical Oncology (2023)

5545 Background: Biomarker driven therapies are increasingly being used for gynecologic cancers, with mirvetuximab soravtansine, a Folate Receptor alpha (FRa) targeting antibody drug conjugate (ADC) being a recent FDA approved agent for patients with FRa positive PROC. Uptifitamab rilsodotin (UpRi) is a late-stage, first in class NaPi2b-targeting ADC with a novel scaffold-linker-payload that enables high drug to antibody ratio and a controlled bystander effect. Approximately 29% of HGSOC patients have FRa positive tumors (Roche VENTANA FOLR1 (FOLR-2.1) RxDx Assay. USPI 2022); ~59% have NaPi2b positive tumors (Okeke et al, USCAP 2022). With the high unmet medical need in PROC and the evolving landscape of available treatments, understanding biomarker expression and correlation between FRa and NaPi2b is critical. Here we evaluate NaPi2b and FRa RNA expression correlation in HGSOC. Methods: Tumor samples (N=84) from the Ph1b UpRi expansion (EXP) cohort were analyzed via Nanostring (770 immune-focus genes from IO 360 panel + 30 customized ADC-related genes) to evaluate the association between NaPi2b and FRa expression. The cutoff for NaPi2b RNA positive or negative was based on approximately 60% of HGSOC patients having NaPi2b positive tumors (top 60% of samples based on expression deemed NaPi2b positive; bottom 40% NaPi2b negative) and FRa RNA cutoff assumed that ~30% of samples were FRa positive. To correlate the NaPi2b expression level between RNA and IHC, the N=84 samples with known expression levels via IHC were analyzed via Nanostring. Results: When evaluating NaPi2b and FRa RNA expression correlation, 21% (N=18) of samples had both NaPi2b positive and FRa positive expression. 38% (N=32) samples were NaPi2b positive and FRa negative. No statistically significant association was observed (Chi-squared test, p=0.129). NaPi2b RNA and IHC expression was evaluated; a statistically significant association was observed (Kappa statistic, p=0.001). Results are in the Table below. Conclusions: Based on this analysis of a limited sample size, there does not appear to be an association between FRa and NaPi2b expression, with the majority of NaPi2b positive samples not being FRa positive. Additionally, general NaPi2b prevalence and the correlation of expression between RNA and IHC suggest that NaPi2b may be a rational biomarker to integrate in RNA tumor panel testing. This research underscores the importance of early, comprehensive testing of all relevant biomarkers to guide therapy selection, and suggests that additional research is needed to evaluate the potential association between FRa and NaPi2b expression via IHC. [Table: see text]
Chemotherapy dose density and effect on prognosis for patients with resectable pancreas cancer: A secondary analysis of SWOG S1505.
Authors: Sameer H. Patel, Sarah Colby, Davendra Sohal, Katherine A Guthrie, Lisa A. Kachnic, E. Gabriela Chiorean, Andrew M. Lowy, Flavio G Rocha, Philip Agop Philip, Syed Ahmad
Journal: Journal of Clinical Oncology (2023)

4158 Background: Chemotherapy is an integral part of multimodality treatment for resectable pancreatic ductal adenocarcinoma (PDAC). Assessing the impact of chemotherapy dose reductions or missed cycles on survival is difficult as few trials prospectively address the prognostic value of this important metric. Methods: SWOG S1505 (NCT02562716) was a randomized, phase II study of perioperative (12 weeks neoadjuvant and 12 weeks adjuvant) chemotherapy with mFOLFIRINOX or gemcitabine/nab-paclitaxel for resectable PDAC. Dose density (DD) was defined as the estimated percent of chemotherapy dose received of the total planned per protocol. Thresholds were based on published analyses and balance in sample size across treatment arms. Cox regression analysis of overall survival (OS) according to DD was performed in patients alive at two landmark time points: after surgery (among those who completed surgery) and at 40 weeks (when protocol therapy was to be completed). Results: Of the 103 eligible patients enrolled, median age was 64 years, 81% underwent pancreaticoduodenectomy, 15% distal pancreatectomy, and 3% a total pancreatectomy. In the 73 patients who underwent surgery, median neoadjuvant chemotherapy DD was 89%. Patients with ≥ 85% DD had higher median OS from surgery (38.1 v. 17.2 months, p = 0.039) compared to patients with &lt; 85% DD. Of the 82 patients who survived to 40 weeks post randomization, 67 underwent surgery and 58 started adjuvant chemotherapy. The median DD for all perioperative chemotherapy was 67%; DD was significantly higher for neoadjuvant compared to adjuvant therapy (83% vs. 58%, p &lt; 0.001). In this cohort, DD ≥ 70% was associated with better median OS from 40 weeks post randomization (32.2 v. 14.0 months, p = 0.017). DD was not significantly associated with pathologic response, margin status, or lymph node negativity. There were no significant differences in DD between the mFOLFIRINOX and gemcitabine/nab-paclitaxel arms. Conclusions: This is the first study to identify a prognostic role for chemotherapy DD in patients undergoing perioperative chemotherapy for resectable PDAC. Patients who received ≥ 85% DD preoperatively and/or ≥70% DD perioperatively had significantly higher mOS than those receiving a smaller proportion of protocol therapy. With greater survival benefit in patients who received higher chemotherapy DD, and higher DD being likelier in preoperative vs. postoperative treatment, these data support use of neoadjuvant chemotherapy for resectable PDAC. Moreover, these findings suggest that DD should be considered in prospective studies for localized PDAC to optimize therapy to be received.
Promoting adherence to germline genetic testing for pancreatic cancer.
Authors: Heather Alison Hannon
Journal: Journal of Clinical Oncology (2023)

e18737 Background: Updated NCCN guidelines support universal germline genetic testing (GGT) for pancreatic ductal adenocarcinoma (PDAC), and literature recommends ordering GGT for PDAC at or near first oncology consult (Chittenden et al., 2021). However, recent studies demonstrate that adherence to updated GGT guidelines for PDAC is poor, and testing rates remain suboptimal (Klatte et al., 2023). A three-month pre-intervention audit (4/2022-6/2022) revealed that less than half of patients diagnosed with PDAC at our community cancer facility underwent GGT in alignment with NCCN guidelines, and only 33% had GGT ordered at the first oncology visit and before treatment. Automated workflows can increase GGT rates for PDAC, but community hospitals may lack infrastructure to support this type of model. Oncology Nurse Navigators (ONN) represent a practical tool for fostering guideline-concordant care for cancer patients treated in the community. The present study explored whether the use of a prompt (or alert message) facilitated by the ONN could change compliance with current recommendations for GGT at a community cancer institute. Methods: We conducted a series of four specific strategies, over a three-month period (7/2022-9/2022). 1. Targeted education was provided to oncologists about NCCN updates. 2. ONN identified newly diagnosed PDAC patients. 3. ONN implemented a prompting process (sending a message to patient’s oncologist within one week of identification of PDAC diagnosis) to review/remind about GGT. 4. Chart review was performed at designated intervals to monitor GGT ordering. The health system’s ONN tracking tool was used to gather, monitor data. Analysis was performed with SPSS software. Results: Nine PDAC patients were identified that met inclusion criteria. Following the ONN prompting intervention there was a 56% increase in PDAC patients who had testing ordered as recommended by NCCN guidelines, a 103% increase in PDAC patients who had GGT ordered at first consult and before treatment initiation. While differences between pre and post intervention were not statistically significant (Fishers Exact Test), the prompting process stimulated valuable discussion between Medical Oncologists (MO) and the ONN, possibly shaping ordering decisions. This included two MOs who switched to ordering GGT at first consult and one MO who had not been planning to order GGT and did so following the prompt. Conclusions: An ONN facilitated prompt offers a simple yet effective means for promoting adherence to GGT guidelines for PDAC in the community setting. ONNs can play a key role in identification of patients and communication and collaboration with MOs before the first oncology consult. The prompting process opens conversation and provides opportunities to clarify, educate about NCCN guidelines in the community setting.
Nivolumab plus cabozantinib in patients with non-clear cell renal cell carcinoma: Updated results from a phase 2 trial.
Authors: Chung-Han Lee, Kelly N. Fitzgerald, Martin H Voss, Maria Isabel Carlo, Andrea Knezevic, Laura Peralta, Ying-Bei Chen, Mark Zucker, Robert A Lefkowitz, Eduard Reznik, Neil J. Shah, Colette Ngozi Owens, Deaglan Joseph McHugh, David H Aggen, Andrew Leonard Laccetti, Ritesh R Kotecha, Darren R. Feldman, Robert J. Motzer
Journal: Journal of Clinical Oncology (2023)

4537 Background: Identification of effective systemic therapy for non-clear cell renal cell carcinoma (RCC) remains a unmet need. We reported a two arm, phase 2 trial of cabozantinib plus nivolumab (CaboNivo) that showed promising efficacy in the treatment arm comprised primarily of papillary and unclassified histology. (Lee, JCO, 40: 2022). Herein, we report updated results with extended follow up. Methods: Patients had advanced non-clear cell RCC, 0 or 1 prior systemic therapies excluding prior immune checkpoint inhibitors, and measurable disease by RECIST. Cabo 40 mg/day plus Nivo 240 mg every 2 weeks or 480 mg every 4 weeks was given for both arms. Arm 1 was comprised of papillary, unclassified, or translocation associated RCC; and Arm 2 had chromophobe RCC (closed early for lack of efficacy). The primary endpoint was objective response rate (ORR) by RECIST; secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. Arm 1 was a single stage design that met its primary endpoint and was expanded to produce more precise estimates of ORR. Correlative analyses by next generation sequencing were performed and will be presented. Results: A total of 40 patients were treated in Arm 1 (data cutoff: Dec 13, 2022). Median follow up time was 34 months (range 20, 51). Twenty-six patients (65%) were previously untreated, and 14 (35%) had 1 prior treatment line: 10 (25%) received prior VEGF-targeted therapy and 8 (20%) received prior mTOR-targeted therapy. ORR is 48% (95% CI 31.5–63.9). Median PFS is 13 months (95% CI: 7, 16). Progression-free survival is 51% (95% CI: 34, 65) at 12 months and 23% (95% CI: 11, 37) at 24 months. Median OS is 28 months (95% CI: 23, 43). Overall survival is 70% (95% CI: 53, 82) at 18 months and 44% (95% CI: 28, 60) at 36 months. PFS and OS were similar for previously treated and untreated patients. For responders, median DOR was 17 months (95% CI: 10, 36). Adverse effects of any grade were experienced by 35 patients (88%); grade 3/4 adverse events were experienced by 22 patients (55%). Grade 3/4 AST and ALT elevations were 18% and 23% respectively. Other common grade 3/4 adverse events were hypertension (5, 13%) and pain (4, 10%). Study therapy was discontinued in 9 patients (28%) for toxicity. Conclusions: Updated results with extended follow-up highlight efficacy and safety for CaboNivo in metastatic non-clear cell RCC pts with papillary, unclassified, or translocation associated histologies. Clinical trial information: NCT03635892 . [Table: see text]
Early changes of PSMA PET signal after initiation of androgen receptor signaling inhibitors in mCRPC: An international multicenter retrospective study.
Authors: Lena Unterrainer, Andrea Farolfi, Florian Rosar, Chloé Santina Denis, Louise Emmett, Ivan de Kouchkovsky, Thomas A. Hope, Masatoshi Hotta, Andrei Gafita, Loic Djaileb, Johannes Czernin, Jeremie Calais
Journal: Journal of Clinical Oncology (2023)

5063 Background: Androgen receptor signaling inhibitors (ARSi) play a relevant role in the treatment of prostate cancer. A potential influence of ARSi on PSMA expression has been described. We evaluated early changes of PSMA-expression by PET in mCRPC patients. Methods: This retrospective study included 5 international sites. Patients with mCRPC undergoing 68 Ga-PSMA-11 PET/CT prior to (PET1) and early after ARSi (PET2 within 29 days maximum) were included. Whole-body (WB) PSMA-positive tumor volume (PSMA-TV) was evaluated using a liver-specific semi-automatically threshold (Affinity 3.0.2, Hermes Medical Solutions). WB PSMA-TV, SUV mean and SUV max and their respective changes (%) were analyzed. PSA changes between PET 1 and PET2 were evaluated. Median values and ranges are provided. Results: 54 patients were included in the analysis. ARSi was initiated 1 day (range 0 – 28) after PET1 while PET2 was performed 14 days (range 7 – 29) after ARSi initiation. PSA at PET1 and PET2 was 9.5 ng/ml (range 0.2 – 490.0) and 8.7 ng/ml (range 0.1 – 732.0), respectively (p = 0.035): -33.0% (range -98% – +496%). The WB PSMA-TV at PET1 and PET2 was 89.9 ml (0.0 – 3097.0) and 112.2 ml (0.0 – 3133.0) ml, respectively (p = 0.016; change of +6.0% (range -88% – +260%). WB PSMA SUV mean and SUV max at PET1 and PET2 was 9.0 (range 5.0 – 43.7) and 9.3 (range 0.0 – 42.5) and 26.5 (range 0.0 – 125.0) and 28.5 (range 0.0 – 212.0), respectively (p = 0.194 and p = 0.353): % change of +3 % (-85% – +71%) and 0% (-55% – +232%). Four of 7 patients with PSA increases at PET2 had an increasing PSMA-TV, 6/7 showed an increasing SUV mean and 5/7 presented with an increased SUV max . Decreasing WB-PSMA-TV in 18/54 (33%) patients was accompanied by decreasing SUVs in 10 of them (56%). Percent PSA change was unrelated to changes in PSMA-TV, SUV mean and SUV max . Conclusions: PSMA-PET performed early after ARSI revealed slight increases in the WB-PSMA-TV, stable WB-PSMA SUVs while serum PSA decreased in most of the patients. We conclude that ARSi does not have a strong effect on PSMA expression within 30 days after treatment initiation. [Table: see text]
Prevalence of STK11, KEAP1, and KRAS mutations/co-mutations and associated clinical outcomes for patients newly diagnosed with metastatic non-small cell lung cancer.
Authors: Firas Dabbous, Ching-Yu Wang, Daniel Simmons, Samuel Huse, Rami Jassim
Journal: Journal of Clinical Oncology (2023)

e21186 Background: Data on the prevalence of emerging mutations /co-mutations (e.g., STK11, KRAS, and KEAP1) and associated clinical outcomes in metastatic non-small cell lung cancer (mNSCLC) patients are lacking therefore the objective of this study is to address these gaps in the current data. Methods: This study used the Flatiron clinico-genomic database and included newly diagnosed patients (≥18 years old) with stage IV NSCLC and known histology/PD-L1 status. Patients enrolled in clinical trials, with positive/missing EGFR or ALK, other malignancies, mixed histology, or without structured data within 90 days of diagnosis were excluded. The prevalence of STK11, KEAP1, KRAS mutations and co-mutations for each combination were evaluated in the overall study cohort and stratified by histology and PD-L1 status ( &gt; or ≤1%). The overall survival (OS) from the date of diagnosis with stage IV was analyzed using Kaplan-Meier methods. Results: Of the 17,020 patients with NSCLC, 964 met the selection criteria and were included in the study. The prevalence of STK11, KEAP1, and KRAS is 18%, 15%, and 35%, respectively. With the exception of KRAS, the prevalence of all selected mutations and the co-mutations is higher in patients with PD-L1 negative and non-squamous NSCLC. The prevalence of KRAS is higher in patients with PD-L1 positive and non-squamous NSCLC (Table). The median OS was 10.1 months (95% CI, 8.6, 11.2) for the overall population, and 6.6 (5.7-8.3), 7.1 (5.8-8.8) and 9.9 (7.6-11.9) months in patients with STK11, KEAP1, and KRAS mutations, respectively. The median OS in patients with co-mutations ranges from 6.1 to 6.7 months. Conclusions: STK11, KEAP1, and KRAS mutations and co-mutations are common in mNSCLC patients. Current treatments, particularly in STK11, KEAP1, and co-mutation patients, are associated with poor OS. To address these harder to treat subgroups new treatment options or clinical trials should be considered. [Table: see text]